Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000038.6(APC):c.847C>T (p.Arg283Ter)

CA015543

184999 (ClinVar)

Gene: APC
Condition: familial adenomatous polyposis 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 34ea9707-51d8-44df-818d-f69b075295c5
Approved on: 2023-02-18
Published on: 2023-03-14

HGVS expressions

NM_000038.6:c.847C>T
NM_000038.6(APC):c.847C>T (p.Arg283Ter)
NC_000005.10:g.112815507C>T
CM000667.2:g.112815507C>T
NC_000005.9:g.112151204C>T
CM000667.1:g.112151204C>T
NC_000005.8:g.112179103C>T
NG_008481.4:g.127987C>T
ENST00000502371.3:c.847C>T
ENST00000504915.3:c.847C>T
ENST00000505084.2:n.903C>T
ENST00000505350.2:c.*853C>T
ENST00000507379.6:c.793C>T
ENST00000509732.6:c.847C>T
ENST00000512211.7:c.847C>T
ENST00000257430.9:c.847C>T
ENST00000257430.8:c.847C>T
ENST00000507379.5:c.793C>T
ENST00000508376.6:c.847C>T
ENST00000508624.5:c.*169C>T
ENST00000512211.6:c.847C>T
NM_000038.5:c.847C>T
NM_001127510.2:c.847C>T
NM_001127511.2:c.793C>T
NM_001354895.1:c.847C>T
NM_001354896.1:c.847C>T
NM_001354897.1:c.877C>T
NM_001354898.1:c.772C>T
NM_001354899.1:c.763C>T
NM_001354900.1:c.670C>T
NM_001354901.1:c.670C>T
NM_001354902.1:c.877C>T
NM_001354903.1:c.847C>T
NM_001354904.1:c.772C>T
NM_001354905.1:c.670C>T
NM_001354906.1:c.-3C>T
NM_001127510.3:c.847C>T
NM_001127511.3:c.793C>T
NM_001354895.2:c.847C>T
NM_001354896.2:c.847C>T
NM_001354897.2:c.877C>T
NM_001354898.2:c.772C>T
NM_001354899.2:c.763C>T
NM_001354900.2:c.670C>T
NM_001354901.2:c.670C>T
NM_001354902.2:c.877C>T
NM_001354903.2:c.847C>T
NM_001354904.2:c.772C>T
NM_001354905.2:c.670C>T
NM_001354906.2:c.-3C>T
More

Pathogenic

Met criteria codes 4
PS4 PVS1 PM2_Supporting PP1_Strong
Not Met criteria codes 11
BP2 BP5 PS2 PM6 PM1 PM3 BA1 BS2 BS1 BS4 BS3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
The c.847C>T (p.Arg283*) variant in APC is a nonsense variant located between codon 49 and 2645 and predicted to cause a premature stop codon in exon 9 in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been reported in 15 probands meeting 8 phenotype points. In addition, this variant is also reported in 50 probands with FAP not otherwise specified, meeting ≥ 16 phenotype points in total (PS4_VeryStrong; PMIDs 30897307, 20924072, 20685668, 10768871, 9950360, 12901799, 11857735, 26625971, 23159591, Bonn internal data). The variant has been reported to segregate with FAP in 5 meioses from 1 family and in 31 members from 1 large FAP family (PP1_Strong; PMID: 12901799, Bonn internal data). The variant is not reported in gnomAD (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: PVS1, PS4_VeryStrong, PM2_Supporting and PP1_Strong (VCEP specifications version 1; date of approval: 12/12/2022).
Met criteria codes
PS4
The variant c.847C>T (p.Arg283Ter) has been reported in at least 15 probands meeting at least 8 phenotype points, there are > 50 probands with FAP but no detailed phenotype information (PS4_VeryStrong); PMIDs 30897307, 20924072,10768871, 9950360, 12901799, Internal data Institute of Human Genetics, Bonn, Germany.
PVS1
The c.847C>T (p.Arg283Ter) variant in APC is a variant to cause a premature stop codon in biologically-relevant-exon 8 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
PP1_Strong
The variant has been reported to segregate with FAP in 5 meioses from 1 family (PMID: 12901799) and the variant was detected in 31 members from 1 large FAP family (PP1_Strong, Internal data Institute of Human Genetics, Bonn, Germany).
Not Met criteria codes
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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